ABSTRACT Posttraumatic stress disorder (PTSD) is a major public health concern that disproportionately effects minorities and those with low-socioeconomic status, such as homeless women, creating a critical health disparity. PTSD has been linked with dysregulated hypothalamic-pituitary-adrenal (HPA) functioning and increased inflammation, which can lead to long-term physical-health problems and PTSD-symptom maintenance, exacerbating disparities. Mindfulness-based interventions, including Mindfulness-based Stress Reduction (MBSR), have shown promise as a complementary tool for addressing PTSD in veterans and with low-income, minority populations, but homeless women have not been examined adequately. MBSR may improve PTSD symptomatology and help modulate the dysregulated stress response common in individuals with PTSD, improving physical and mental health concurrently. This project proposes a mixed-methods, open-label, parallel, randomized-clinical trial of a modified-MBSR intervention to reduce PTSD symptoms in homeless women and to explore physiological correlates of treatment-response. Inclusion criteria will be currently homeless women, age 18-64, with clinically-significant PTSD as defined by standard guidelines. Phase I will be a qualitative study to refine MBSR for cultural-appropriateness in a high-minority community and to address the specific needs of homeless women. In Phase II, participants will be randomly assigned to the MBSR-based intervention or a health promotion attention-control group. At baseline, women will complete psychosocial assessments (e.g., depression, substance use, trauma history) and participate in a brief stress task, providing salivary samples before and after the task (which will be assayed for cortisol and C-reactive protein, a marker of inflammation). Women will then participate in the 9-week MBSR-based program or health-promotion control group. Follow-up assessments that include psychosocial and biological data will occur immediately after final intervention session and again 6-months later. Clinically-meaningful improvements in PTSD (primary outcome) and secondary outcomes (e.g., depression, substance use, inflammation, cortisol reactivity) will then be examined. The candidate?s training plan capitalizes on the expertise of a diverse mentoring team, integrating advanced training in mixed-methods research, community-based clinical trials, mindfulness-based interventions, and salivary biosciences. The plan includes didactic courses and on-one-one mentoring at the University of California, Irvine (mixed-methods, qualitative design, clinical trials, and salivary bioscience) and Loma Linda University (MBIs), both in Southern California. The training plan also includes in-depth workshops in each substantive area and in training in the responsible conduct of research. The candidate will complete the K01 with expertise in mixed- methods, biopsychosocial approaches to address PTSD in populations with high health-disparities.